We have investigated the translocation of immunoglobulins across epithelia by in vitro studies with cultured colon neoplastic cells and immunoelectromicroscopy with peroxidase-labeled antibodies and antigens. The colon cells were shown to have the characteristic polarity of mature epithelial cells and the secretory component (SC) on basolateral plasma membranes. When the cells were incubated with peroxidase-labeled dimeric human IgA at 0 degrees, the immunoglobulin bound specifically to SC. Upon incubation at 37 degrees, the bound IgA entered the cells by pinocytosis and was transported apically through the cytoplasm in vesicles. IgA was discharged at the apical surface after about 30 minutes. We conclude that translocation of dimeric IgA by epithelial cells in vitro involves: 1) binding to SC, 2) pinocytosis, 3) transcytoplasmic migration in vesicles, and 4) discharge at the apical surface. Ultrastructural correlates of these steps have been observed in immunoelectronmicroscopic studies of human intestinal epithelium. Therefore, the epithelial translocation of dimeric IgA in vivo appears to be analagous to that seen in vitro.